Fairlie Reese's research while affiliated with University of California, Irvine and other places

Publications (13)

Preprint
Full-text available
Biological systems are immensely complex, organized into a multi-scale hierarchy of functional units based on tightly-regulated interactions between distinct molecules, cells, organs, and organisms. While experimental methods enable transcriptome-wide measurements across millions of cells, the most ubiquitous bioinformatic tools do not support syst...
Preprint
Full-text available
Motivation Weighted gene co-expression network analysis (WGCNA) is frequently used to identify modules of genes that are co-expressed across many RNA-seq samples. However, the current R implementation is slow, not designed to compare modules between multiple WGCNA networks, and results are hard to interpret and visualize. We introduce the PyWGCNA P...
Preprint
Full-text available
Using third-generation sequencers, long-read RNA-seq is increasingly applied in transcriptomic studies given its major advantage in characterizing full-length transcripts. A number of methods have been developed to analyze this new type of data for transcript isoforms and their abundance. Another application, which is significantly under-explored,...
Article
Accurate transcription start site (TSS) annotations are essential for understanding transcriptional regulation and its role in human disease. Gene collections such as GENCODE contain annotations for tens of thousands of TSSs, but not all of these annotations are experimentally validated, nor do they contain information on cell type-specific usage....
Article
Full-text available
The rise in throughput and quality of long-read sequencing should allow unambiguous identification of full-length transcript isoforms. However, its application to single-cell RNA-seq has been limited by throughput and expense. Here we develop and characterize long-read Split-seq (LR-Split-seq), which uses combinatorial barcoding to sequence single...
Preprint
Full-text available
With increased usage of long-read sequencing technologies to perform transcriptome analyses, there becomes a greater need to evaluate different methodologies including library preparation, sequencing platform, and computational analysis tools. Here, we report the study design of a community effort called the Long-read RNA-Seq Genome Annotation Asse...
Preprint
Full-text available
Accurate transcription start site (TSS) annotations are essential for understanding transcriptional regulation and its role in human disease. Gene collections such as GENCODE contain annotations for tens of thousands of TSSs, but not all of these annotations are experimentally validated nor do they contain information on cell type-specific usage. T...
Preprint
Full-text available
Alternative RNA isoforms are defined by promoter choice, alternative splicing, and polyA site selection. Although differential isoform expression is known to play a large regulatory role in eukaryotes, it has proved challenging to study with standard short-read RNA-seq because of the uncertainties it leaves about the full-length structure and preci...
Article
Full-text available
Motivation: Long-read RNA-sequencing technologies such as PacBio and Oxford Nanopore have discovered an explosion of new transcript isoforms that are difficult to visually analyze using currently available tools. We introduce the Swan Python library, which is designed to analyze and visualize transcript models. Results: Swan finds 4,909 differen...
Preprint
Full-text available
Motivation Long-read RNA-sequencing technologies such as PacBio and Oxford Nanopore have discovered an explosion of new transcript isoforms that are difficult to visually analyze using currently available tools. We introduce the Swan Python library, which is designed to analyze and visualize transcript models. Results Swan finds 4,909 differential...
Article
Pre-mRNA splicing is regulated through multiple trans-acting splicing factors. These regulators interact with the pre-mRNA at intronic and exonic positions. Given that most exons are protein coding, the evolution of exons must be modulated by a combination of selective coding and splicing pressures. It has previously been demonstrated that selectiv...
Article
Alternative splicing is widely acknowledged to be a crucial regulator of gene expression and is a key contributor to both normal developmental processes and disease states. While cost-effective and accurate for quantification, short-read RNA-seq lacks the ability to resolve full-length transcript isoforms despite increasingly sophisticated computat...
Preprint
Full-text available
Alternative splicing is widely acknowledged to be a crucial regulator of gene expression and is a key contributor to both normal developmental processes and disease states. While cost-effective and accurate for quantification, short-read RNA-seq lacks the ability to resolve full-length transcript isoforms despite increasingly sophisticated computat...

Citations

... Alternative UTR isoform usage is an important post-transcriptional regulatory mechanism in many physiological and pathological processes, affecting the rate of RNA degradation and the status of translation [276,277]. Currently, many research groups have been combining scRNA-seq with long-read sequencing technologies to enable high-confidence isoform profiling at the single-cell level [278][279][280]. Such studies have paved the way for the examination of alternative splicing and transcript fusions between cells and/ or cell types, as well as during the progression of diseases [278]. ...
... The ability of long read RNA-Seq to generate reads corresponding to full-length transcripts provides an opportunity to discover novel transcripts and thereby enable the quantification of isoform expression using context-specific annotations 16 . Tools such as FLAIR 17 , TALON 18 , or StringTie2 19 have been developed for transcript discovery from long read RNA-Seq and have been shown to identify novel transcripts even in well annotated genomes. ...
... Different isoforms of the histone H3.3 subunit gene H3f3b were hubs for modules RGL-M1 and RGL-M11, which were associated with ependymal and neuronal cell fates respectively, suggesting that alternative TES usage in H3f3b plays a role in regulating epigenetic factors in murine hippocampal development (Fig. 3f). Cd9 encodes a transmembrane protein and is a known glioblastoma biomarker (35), and we found subtle differences in the TSS between hub isoforms in modules RGL-M6 and RGL-M9 that we show as a splicing summary graph (25) (Fig. 3i), supporting functional changes mediated by small isoform differences. ...
... Another crucial factor in splice site selection is the genomic architecture [9][10][11][12]. The genomes in lower eukaryotes are characterized almost exclusively by the presence of short introns (<250 nts). ...
... However as these parameters are dependent on sequencing depth, the same threshold can generate vastly different results across multiple samples [21][22][23] . This can partially be addressed with additional thresholds such as a minimum relative isoform expression or transcripts-per-million. ...
... The ability of long read RNA-Seq to generate reads corresponding to full-length transcripts provides an opportunity to discover novel transcripts and thereby enable the quantification of isoform expression using context-specific annotations 16 . Tools such as FLAIR 17 , TALON 18 , or StringTie2 19 have been developed for transcript discovery from long read RNA-Seq and have been shown to identify novel transcripts even in well annotated genomes. However, RNA degradation, sequencing, and alignment artefacts can introduce false positive transcript candidates and impact quantification 20 . ...